The amyloidoses are diseases that result from errors in protein folding. When new proteins are made, their peptide chains normally fold into the correct shape. Sometimes, however, the peptide chains fold incorrectly and form highly stable β-sheets that are insoluble and resistant to proteolytic digestion. When this insoluble protein is deposited in tissues, it is called amyloid. Amyloid proteins may be deposited in a localized fashion or widely distributed throughout the body. They cause damage by displacing normal cells. If critical organs such as the kidneys, liver, or heart are extensively disrupted, the disease may be fatal. Amyloidosis can affect all domestic mammals, and minor, asymptomatic deposition of amyloid proteins is common in aged animals.
The most common form of amyloid is generated by misfolding of the major acute-phase protein, serum amyloid A (SAA). Levels of SAA in the blood climb significantly in animals with severe inflammation. If SAA fails to fold correctly, it forms a very stable protein called AA amyloid. Amyloidosis thus develops as a result of chronic inflammatory diseases, chronic bacterial infections, and malignant tumors. It is a common cause of death in horses aggressively immunized for antiserum production. AA amyloid is usually deposited in parenchymal organs, such as the spleen, where it may not cause clinical signs. If the kidneys are involved, the presence of amyloid in glomeruli may lead to severe proteinuria, eventually resulting in renal failure and death. There is no practical treatment for this form of amyloidosis, although removal of the source of inflammation may slow amyloid deposition and hence progression of the disease.
Misfolding of immunoglobulin light chains generates a second form of amyloid, AL amyloid. This commonly results from the overproduction of monoclonal light chains in animals with plasma cell tumors (myelomas). AL amyloid tends to be deposited in mesenchymal tissues, especially nervous tissues and joints. It is rare in domestic animals.
At least 20 other proteins have been shown to misfold, form β-sheets, and become deposited in the tissues as amyloid. There are also hereditary amyloidoses, such as those described in Abyssinian cats and Chinese Shar-Pei dogs, in which mutations result in protein misfolding. Some amyloid is formed in all aged animals (senile systemic amyloidosis); eg, in aged dogs, amyloid is commonly deposited in the media of meningeal and cortical arteries. Tumor-like amyloid nodules and subcutaneous amyloid have been reported in horses.
Some forms of amyloid may be transmitted between animals. The most important of these are the transmissible spongiform encephalopathies, such as bovine spongiform encephalopathy (see Bovine Spongiform Encephalopathy) and scrapie (see Scrapie). These are caused by the production of misfolded prion proteins. Indeed, even AA amyloid is somewhat transmissible, because experimental administration of small amounts of amyloid protein to an animal can accelerate its development. Cheetahs are especially prone to amyloidosis and shed an infectious form of amyloid protein in their feces.
Because of its diffuse distribution and insidious onset, amyloidosis is difficult to diagnose clinically. However, amyloidosis should be suspected if progressive renal or hepatic failure develops in animals subsequent to chronic infections or inflammation. There is no specific therapy that can prevent the development of amyloidosis or promote the resorption of fibrils. Animals with persistent inflammation should be treated to reduce the severity of their inflammatory response and hence the availability of SAA. Amyloidosis is readily recognized at necropsy and in histologic sections by its affinity for dyes such as Congo red.
Last full review/revision August 2013 by Ian Tizard, BVMS, PhD, DACVM